Gene Therapy for Alpha 1- Antitrypsin Deficiency

Inclusion Criteria:

* AAT genotype ZZ, or Z null heterozygotes, and if on augmentation therapy, pre-therapy AAT serum levels \<11 μM
* Evidence of mild to moderate disease by the following lung function parameters on PFT and/or chest high resolution computational tomography (HRCT)

  * Emphysema as assessed by HRCT and/or
  * Lung function parameters consistent with mild to moderate loss of lung function, in either category 1 or category 2 below:

    1. Mild lung dysfunction: FEV1/FVC \< 0.70 and FEV1 ≥ 80% predicted
    2. Moderate lung dysfunction: FEV1/FVC \< 0.70 and FEV1 40 - \< 80% predicted and DLCO \<80% predicted.
* Troponin T within normal limits
* Normal liver ultrasound and serum alpha fetoprotein
* Normal kidney function
* No contraindications to receiving corticosteroid immunosuppression

Exclusion Criteria:

* Individuals receiving chronic (used daily for greater than 30 days) systemic corticosteroids or other immunosuppressive medications for pre-existing conditions (inhaled corticosteroids for pulmonary associated issues are permitted)
* Inability to tolerate immunosuppression with corticosteroids (e.g., uncontrolled diabetes)
* Individuals with an immunodeficiency disease, or evidence of active infection of any type, including human immunodeficiency virus
* Evidence of major central nervous system, major psychiatric, musculoskeletal or immune disorder
* Prior history of myocardial infarction or cancer within the past 5 years (other than basal cell carcinoma of the skin)
* Decompensated heart failure (NY4A class III-IV at time of baseline clinical assessment)
* Abnormal ECG at screening with findings consistent with cardiac disease
* Females who are currently pregnant or lactating
* Individuals receiving experimental medications or participating in another experimental protocol for at least 3 months prior to entry to the study
* Use of oxygen supplementation
* Risk for thromboembolic disease
* History of significant cardiovascular disease, hypertension, prior myocardial infarction and/or cerebrovascular event
* Individuals who are currently on beta-blockers, or other cardiac therapy related drugs
* Prior history of hypersensitivity or anaphylaxis associated with the administration of any AAT product